Chronic Diseases and Translational Medicine最新文献

Bone disease is the most common complication in patients with multiple myeloma (MM), and it may lead to skeletal-related events (SREs) such as bone pain, pathological fractures, and spinal cord compression, which impair a patients' quality of life and survival. The pathogenesis of myeloma bone disease (MBD) involves disruption of bone reconstitution balance including excessive activation of osteoclasts, inhibition of osteoblasts, and participation of osteocytes and bone marrow stromal cells. Various factors, such as the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG), dickkopf-1 (DKK-1), sclerostin, and activin-A, are involved in the development of MBD. Bisphosphonates and the anti-RANKL antibody denosumab are currently the main treatment options for MBD, delaying the onset of SREs. Denosumab is preferred in patients with MM and renal dysfunction. Although effective drugs have been approved, antimyeloma therapy is the most important method for controlling bone disease.

Gastrointestinal cancers are difficult to be cured with a high recurrence rate accounting for more than 50% of global cancer-related morbidity and mortality.¹ Many patients with gastrointestinal cancer are diagnosed at a late stage. Over the past few decades, basic and clinical research with new technologies have made significant progress in the diagnosis and treatment of gastrointestinal cancers, which significantly improved the quality of life and prolonged the survival of patients. Here, we briefly highlight several advances in diagnosing and treating gastrointestinal tumors, mainly gastric cancer and colorectal cancer from multiple perspectives.

Early diagnosis is crucial for the treatment of gastrointestinal cancers. With the continuous advances in molecular biology, genomics, and epigenetics, individualized diagnosis of gastric cancer and colorectal cancer holds promise for basic research and clinical applications. Liquid biopsy, including detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), tumor-related extracellular vesicles (exosomes and microvesicles), tumor-educated platelets, proteins as well as metabolites in a range of bodily fluids offers a cost-efficient and noninvasive approach to screening tumor and monitor relapse and response to treatment.² CTCs are tumor cells in peripheral blood, falling off from the solid tumor focus (primary focus or metastatic focus) due to spontaneous or diagnostic and treatment procedures.³ Most of the CTCs undergo apoptosis or phagocytosis and are engulfed by immune cells after entering the peripheral blood; only a few can escape and invade a distant organ to form metastatic foci, increasing the risk of death in patients with gastrointestinal cancers.³ Recent studies have shown that CTCs are heterogenic and can proliferate in vivo and in vitro. These, together with the findings from the single-cell molecular analysis, have provided unique insights into the biology of cancer metastasis and therapeutic response.

ctDNA may reflect tumor-specific abnormalities, and analysis of ctDNA can be applied in the diagnosis, therapeutic response, and prognosis of cancer patients. The mutations in specific genes have been detected in the plasma of patients with several types of gastrointestinal cancers, suggesting that ctDNA may be a possible biomarker of gastrointestinal cancers. The minimal residual disease (MRD) is a microscopic focus of treatment-insensitive tumor cells or the early recurrence of tumors.⁴ Hence, precise evaluation of MRD is especially significant during or after the treatment of gastrointestinal tumors.⁵ The detection of ctDNA and CTCs can help identify and explain the nature of MRD and may provide a new strategy for the prevention and treatment of tumor metastasis.^{3, 5} Neverthel

In a 2012 study, occasional and low cumulative cannabis use was not associated with adverse effects on pulmonary function.¹ With tobacco, the more used, the more loss of air flow rate and lung volume. The same was not true with cannabis use. Air flow rate increased rather than decreased with increased exposure to cannabis up to a certain level.

An important factor that helped explain the difference in effects from tobacco and cannabis was the amount of each that was smoked. Tobacco users typically smoked 10–20 cigarettes daily, some even more. Cannabis smokers, on average, smoked only two to three times a month, so the average exposure to cannabis was much lower than for tobacco. People experiment with cannabis in their late teens and 20s, and some consume relatively low levels for years. Although heavy exposure to cannabis might damage the lungs, reliable estimates of the effects of heavy use were not available in the 2012 study, as heavy users were relatively rare in the study population.

In the current analysis, we used data from UK Biobank (UKB) to assess the effect of cannabis on coronavirus disease (COVID-19) infection and to determine whether cannabis lung damage might facilitate COVID-19 infection in formerly heavy users.

The UKB is a large prospective observational study comprising about 500,000 men and women (N = 229,134 men, N = 273,402 women), more than 90% White, aged 40–69 years at enrollment. Participants were recruited from across 22 centers located throughout England, Wales, and Scotland, between 2006 and 2010, and continue to be longitudinally followed for capture of subsequent health events.² This methodology is like that of the Framingham Heart Study,³ with the exception that the UKB program collects postmortem samples, which Framingham did not.

Our UKB application was approved as UKB project 57,245 (S.L. and P.H.R.).

Doctor-diagnosed chronic obstructive pulmonary disease (COPD) is from UKB data field 22,130. At enrollment, the subject was asked on a touchscreen, “Has a doctor ever told you that you have had any of the conditions below?” COPD was one of the options listed.

The subject was asked, “Have you taken cannabis (marijuana, grass, hash, ganja, blow, draw, skunk, weed, spliff, dope), even if it was a long time ago?” If the answer was “yes,” cannabis use was recorded in the UKB data field 20,454, maximum frequency of taking cannabis, question asked: “Considering when you were taking cannabis most regularly, how often did you take it?” Answers were 1 = Less than once a month, 2 = Once a month or more, but not every week, 3 = Once a week or more, but not every day, and 4 = Every day. Subject was then asked (UKB data field 20455) “About how old were you when you last had cannabis?”

All UKB subjects who had cannabis-use data, COVID-19 test data, and COPD data were incl

Breast cancer (BC) is the most prevalent malignancy worldwide, and a continued upward trend has been predicted in the coming decades. Screening in selected targeted populations, which is effective in reducing cancer-related mortality, has been widely implemented in many countries. This review summarizes the advances in BC screening techniques, organized or opportunistic BC screening programs across different countries, and screening modalities recommended by different academic authorities. Mammography is the most widely used and effective technique for BC screening. Other complementary techniques include ultrasound, clinical breast examination, and magnetic resonance imaging. Novel screening tests, including digital breast tomosynthesis and liquid biopsies, are still under development. Globally, the implementation status of BC screening programs is uneven, which is reflected by differences in screening modes, techniques, and population coverage. The recommended optimal screening strategies varied according to the authoritative guidelines. The effectiveness of current screening programs is influenced by several factors, including low detection rate, high false-positive rate, and unsatisfactory coverage and uptake rates. Exploration of accurate BC risk prediction models and the development of risk-stratified screening strategies are highly warranted in future research.